neuromedin-n and Stroke

The peptide neurotensin is implicated in insulin resistance, diabetes mellitus (DM), and cardiovascular disease.. We studied the association of neurotensin's stable precursor, pro-neurotensin/neuromedin N (pro-NT/NMN) with incident metabolic syndrome (MetS) and DM.. We included 3772 participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who completed the baseline exam (2003-2007), the follow-up exam (2013-2016), and had pro-NT/NMN measured by immunoassay. Weighted logistic regression models were fitted to incident DM, incident MetS, and each MetS component, separately, incorporating demographics, metabolic risk factors, homeostasis model of insulin resistance (HOMA-IR), and diet scores. Incident MetS was defined by 3 or more harmonized criteria at follow-up in those with fewer than 3 at baseline. Incident DM was defined by use of hypoglycemic drugs/insulin, fasting glucose 126 mg/dL or greater, or random glucose 200 mg/dL or greater in those without these at baseline.. Median (IQR) plasma pro-NT/NMN was 160 pmol/L (118-218 pmol/L). A total of 564 (of 2770 without baseline MetS) participants developed MetS, and 407 (of 3030 without baseline DM) developed DM. Per SD higher log-pro-NT/NMN, the demographic-adjusted odds ratio (OR) and 95% CI of incident MetS was 1.22 (1.11-1.35), 1.16 (1.00-1.35) for incident low high-density lipoprotein (HDL), and 1.25 (1.11-1.40) for incident dysglycemia. The association of pro-NT/NMN with MetS was attenuated in the model adding HOMA-IR (OR per SD log-pro-NT/NMN 1.14; 95% CI, 1.00-1.30). There was no association with incident DM (OR per SD log-pro-NT/NMN 1.06; 95% CI, 0.94-1.19).. Pro-NT/NMN was associated with MetS and 2 components, dysglycemia and low HDL, likely explained by insulin resistance.

Topics: Blood Glucose; Case-Control Studies; Cohort Studies; Diabetes Mellitus; Diet; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Neurotensin; Peptide Fragments; Risk Factors; Stroke

The neuropeptide neurotensin (NT) has been linked to cardiometabolic disease. Cardiovascular risk factors are being recognized as risk factors for cognitive impairment.. To examine the association of the stable precursor of NT, pro-neurotensin/neuromedin N (pro-NT/NMN), with incident cognitive impairment (ICI).. We conducted a prospective nested case-control study in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. In 2003-2007, REGARDS enrolled 30,239 Black and White adults aged ≥45 years. ICI was identified using a 3-test cognitive battery administered biannually. Baseline pro-NT/NMN was measured by immunoassay in 393 cases of ICI and 490 controls after 3.4 years follow up. Multivariable logistic regression was used to calculate odds ratios (OR) of ICI by pro-NT/NMN quartiles. Race, age, and sex differences were studied with stratified models and interaction testing.. Pro-NT/NMN was higher in Black participants and those with hypertension and diabetes. Women with a 4th versus 1st-quartile pro-NT/NMN had 2.28-fold increased odds of ICI (95% CI 1.08-4.78) after adjusting for risk factors and incident stroke. There was no association of higher pro-NT/NMN quartiles with ICI in the overall group or men. There were no race or age differences in associations.. In this biracial population-based study, elevated systemic pro-NT/NMN was associated with more than doubled risk of ICI in women but not men. Others reported sex-specific associations in women for cardiovascular mortality and diabetes with higher pro-NT/NMN, supporting a role for future research on sex differences in the neurotensinergic system.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Cognitive Dysfunction; Cohort Studies; Female; Humans; Male; Middle Aged; Neurotensin; Peptide Fragments; Prospective Studies; Risk Factors; Sex Factors; Stroke